Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk

Overview

Journal J Am Coll Cardiol

Specialty Cardiology & Vascular Diseases

Date 2023 Jun 14

PMID 37316112

Authors

Kenechukwu Mezue

Michael T Osborne

Shady Abohashem

Hadil Zureigat

Charbel Gharios

Simran S Grewal

Azar Radfar

Alexander Cardeiro

Taimur Abbasi

Karmel W Choi

Zahi A Fayad

Jordan W Smoller

Rachel Rosovsky

Lisa Shin

Roger Pitman

Ahmed Tawakol

Affiliations

Soon will be listed here.

Abstract

Background: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (AC) has been linked to lower MACE risk, but the mechanisms are unclear.

Objectives: The purpose of this study was to evaluate whether the association between AC and MACE is mediated by decreased SNA.

Methods: Individuals enrolled in the Mass General Brigham Biobank who completed a health behavior survey were studied. A subset underwent F-fluorodeoxyglucose positron emission tomography, enabling assessment of SNA. Alcohol consumption was classified as none/minimal, light/moderate, or high (<1, 1-14, or >14 drinks/week, respectively).

Results: Of 53,064 participants (median age 60 years, 60% women), 23,920 had no/minimal alcohol consumption and 27,053 AC. Over a median follow-up of 3.4 years, 1,914 experienced MACE. AC (vs none/minimal) associated with lower MACE risk (HR: 0.786; 95% CI: 0.717-0.862; P < 0.0001) after adjusting for cardiovascular risk factors. In 713 participants with brain imaging, AC (vs none/minimal) associated with decreased SNA (standardized beta -0.192; 95% CI: -0.338 to -0.046; P = 0.01). Lower SNA partially mediated the beneficial effect of AC on MACE (log OR: -0.040; 95% CI: -0.097 to -0.003; P < 0.05). Further, AC associated with larger decreases in MACE risk among individuals with (vs without) prior anxiety (HR: 0.60 [95% CI: 0.50-0.72] vs 0.78 [95% CI: 0.73-0.80]; P interaction = 0.003).

Conclusions: AC associates with reduced MACE risk, in part, by lowering activity of a stress-related brain network known for its association with cardiovascular disease. Given alcohol's potential health detriments, new interventions with similar effects on SNA are needed.

Citing Articles

Accelerated development of cardiovascular risk factors mediates risk for major adverse cardiovascular events in posttraumatic stress disorder.

Khalil M, Sinnott S, Civieri G, Abohashem S, Grewal S, Hanlon E Brain Behav Immun. 2024; 125:148-157.

PMID: 39733862 PMC: 11903154. DOI: 10.1016/j.bbi.2024.12.155.

Association of resting amygdalar activity with persistent atrial fibrillation mediated by right atrial inflammation activity on F-fluorodeoxyglucose positron emission tomography-computed tomography.

Yu W, Wang C, Yue Y, Sun F, Wan P, Shao S Quant Imaging Med Surg. 2024; 14(12):8294-8307.

PMID: 39698660 PMC: 11652025. DOI: 10.21037/qims-24-728.

A nonlinear relationship between alcohol consumption and cognitive function in elderly people: a population-based study from NHANES 2011-2014.

Chen K, Li Y, Yue R, Jin Z, Cui S, Zhang X Front Aging Neurosci. 2024; 16:1458274.

PMID: 39654808 PMC: 11626387. DOI: 10.3389/fnagi.2024.1458274.

Association of alcohol consumption with aortic aneurysm and dissection risk: results from the UK Biobank cohort study.

Liang Y, Zou G, Wang D, Zeng W, Zhang J, Huang X World J Emerg Med. 2024; 15(6):465-474.

PMID: 39600819 PMC: 11586140. DOI: 10.5847/wjem.j.1920-8642.2024.096.

Additive effect of high transportation noise exposure and socioeconomic deprivation on stress-associated neural activity, atherosclerotic inflammation, and cardiovascular disease events.

Abohashem S, Aldosoky W, Hahad O, Civieri G, Assefa A, Lau H J Expo Sci Environ Epidemiol. 2024; 35(1):62-69.

PMID: 39578565 PMC: 11875943. DOI: 10.1038/s41370-024-00734-2.

References

Fox A, Oler J, Shelton S, Nanda S, Davidson R, Roseboom P . Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates. Proc Natl Acad Sci U S A. 2012; 109(44):18108-13. PMC: 3497741. DOI: 10.1073/pnas.1206723109. View

DAgostino Sr R, Vasan R, Pencina M, Wolf P, Cobain M, Massaro J . General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008; 117(6):743-53. DOI: 10.1161/CIRCULATIONAHA.107.699579. View

Zahr N, Kaufman K, Harper C . Clinical and pathological features of alcohol-related brain damage. Nat Rev Neurol. 2011; 7(5):284-94. PMC: 8121189. DOI: 10.1038/nrneurol.2011.42. View

Tawakol A, Ishai A, Takx R, Figueroa A, Ali A, Kaiser Y . Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017; 389(10071):834-845. PMC: 7864285. DOI: 10.1016/S0140-6736(16)31714-7. View

Castro V, Gainer V, Wattanasin N, Benoit B, Cagan A, Ghosh B . The Mass General Brigham Biobank Portal: an i2b2-based data repository linking disparate and high-dimensional patient data to support multimodal analytics. J Am Med Inform Assoc. 2021; 29(4):643-651. PMC: 8922162. DOI: 10.1093/jamia/ocab264. View

Gorka S, Fitzgerald D, King A, Phan K . Alcohol attenuates amygdala-frontal connectivity during processing social signals in heavy social drinkers: a preliminary pharmaco-fMRI study. Psychopharmacology (Berl). 2013; 229(1):141-54. PMC: 3740023. DOI: 10.1007/s00213-013-3090-0. View

Xi B, Veeranki S, Zhao M, Ma C, Yan Y, Mi J . Relationship of Alcohol Consumption to All-Cause, Cardiovascular, and Cancer-Related Mortality in U.S. Adults. J Am Coll Cardiol. 2017; 70(8):913-922. DOI: 10.1016/j.jacc.2017.06.054. View

Brien S, Ronksley P, Turner B, Mukamal K, Ghali W . Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ. 2011; 342:d636. PMC: 3043110. DOI: 10.1136/bmj.d636. View

He C, Gong L, Yin Y, Yuan Y, Zhang H, Lv L . Amygdala connectivity mediates the association between anxiety and depression in patients with major depressive disorder. Brain Imaging Behav. 2018; 13(4):1146-1159. DOI: 10.1007/s11682-018-9923-z. View

10.

Liu W, Zhang W, Zheng Z, Zou J, Liu X, Huang S . Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety. Nat Commun. 2020; 11(1):2221. PMC: 7203160. DOI: 10.1038/s41467-020-15920-7. View

11.

Motzkin J, Philippi C, Wolf R, Baskaya M, Koenigs M . Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biol Psychiatry. 2014; 77(3):276-284. PMC: 4145052. DOI: 10.1016/j.biopsych.2014.02.014. View

12.

Ruitenberg A, Van Swieten J, Witteman J, Mehta K, Van Duijn C, Hofman A . Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet. 2002; 359(9303):281-6. DOI: 10.1016/S0140-6736(02)07493-7. View

13.

Biddinger K, Emdin C, Haas M, Wang M, Hindy G, Ellinor P . Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022; 5(3):e223849. PMC: 8956974. DOI: 10.1001/jamanetworkopen.2022.3849. View

14.

Goyal A, Dey A, Chaturvedi A, Elnabawi Y, Aberra T, Chung J . Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in Psoriasis: A Prospective Cohort Study. JACC Cardiovasc Imaging. 2018; 13(2 Pt 1):465-477. PMC: 6506409. DOI: 10.1016/j.jcmg.2018.08.038. View

15.

Costanzo S, Di Castelnuovo A, Donati M, Iacoviello L, de Gaetano G . Alcohol consumption and mortality in patients with cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2010; 55(13):1339-47. DOI: 10.1016/j.jacc.2010.01.006. View

16.

Fillmore K, Stockwell T, Chikritzhs T, Bostrom A, Kerr W . Moderate alcohol use and reduced mortality risk: systematic error in prospective studies and new hypotheses. Ann Epidemiol. 2007; 17(5 Suppl):S16-23. DOI: 10.1016/j.annepidem.2007.01.005. View

17.

Nagel M, Jansen P, Stringer S, Watanabe K, de Leeuw C, Bryois J . Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways. Nat Genet. 2018; 50(7):920-927. DOI: 10.1038/s41588-018-0151-7. View

18.

Charlson M, Pompei P, Ales K, MacKenzie C . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373-83. DOI: 10.1016/0021-9681(87)90171-8. View

19.

de Moor M, van den Berg S, Verweij K, Krueger R, Luciano M, Arias Vasquez A . Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder. JAMA Psychiatry. 2015; 72(7):642-50. PMC: 4667957. DOI: 10.1001/jamapsychiatry.2015.0554. View

20.

Wood A, Kaptoge S, Butterworth A, Willeit P, Warnakula S, Bolton T . Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. 2018; 391(10129):1513-1523. PMC: 5899998. DOI: 10.1016/S0140-6736(18)30134-X. View